Approximately 1% of the U.S. population has a urinary stone annually. Some 15-50% of these stones are caused by infection. Infected stones are frequently refractory to treatment by the best medical and surgical means. Experimental studies have shown that struvite and carbonate apatite urinary stones caused by infection form primarily as a consequence of the bacterial enzyme, urease. Urease hydrolyzes urea; the resulting alkalinity and hyperammoniuria cause urinary supersaturation with respect to magnesium phosphate and calcium phosphate. Acetohydroxamic acid (AHA) is an effective inhibitor of bacterial urease; its pharmacologic characteristics are favorable for human use. AHA has been shown to maintain urine in an undersaturated state in the presence of urease-producing bacteria; in these studies stone growth was prevented, and preformed struvite and apatite crystals dissolved. In preliminary clinical trials, AHA has been administered to patients who have chronic urinary infection associated with stones. Urine alkalinity and supersaturation have been eliminated. No toxicity has been observed. The proposed research will investigate the absorption, distribution, metabolism and excretion pharmacokinetics of AHA in rats, and will attempt to define the pharmacokinetics of AHA in man. Since urinary stones caused by infection are recalcitrant to current modalities of medical and surgical management, successful treatment with AHA may reduce the morbidity and mortality currently sustained by the more than 80% of patients with recurrent "infection stones." The proposed studies will attempt to provide some of this information.